Hayashi Yujiro
Department of Chemistry, Graduate School of Science, Tohoku University, 6-3 Aramaki Aza-Aoba, Aoba-ku, Sendai, Miyagi, 980-8578, Japan.
Chem Rec. 2023 Jul;23(7):e202200159. doi: 10.1002/tcr.202200159. Epub 2022 Jul 27.
The aldol reaction is one of the most important carbon-carbon bond-forming reactions in organic chemistry. Asymmetric direct cross-aldol reaction of two different aldehydes has been regarded as a difficult reaction because of the side reactions such as self-aldol reaction and over reaction. We found that trifluoromethyl-substituted diarylprolinol, α,α-bis[3,5-bis(trifluoromethyl)phenyl]-2-pyrrolidinemethanol (1), is an effective organocatalyst that promotes several cross-aldol reactions of aldehydes with excellent diastereo- and enantioselectivities. Acetaldehyde can be employed as a suitable nucleophilic aldehyde. Successful electrophilic aldehydes are ethyl glyoxylate, chloroacetaldehyde, dichloroacetaldehyde, chloral, α-alkyl-α-oxo aldehyde, trifluoroacetaldehyde, glyoxal, alkenyl aldehyde, alkynyl aldehyde, and formaldehyde. Some of the aldehydes are commercially available as a polymer solution, an aqueous solution, or in the hydrated form. They can be used directly in the asymmetric aldol reaction as a commercially available form, which is a synthetic advantage. Given that the obtained aldol products possess several functional groups along with a formyl moiety, they are synthetically useful chiral building blocks.
羟醛缩合反应是有机化学中最重要的碳-碳键形成反应之一。由于存在诸如自身羟醛缩合反应和过度反应等副反应，两种不同醛的不对称直接交叉羟醛缩合反应一直被视为一项困难的反应。我们发现，三氟甲基取代的二芳基脯氨醇，即α,α-双[3,5-双（三氟甲基）苯基]-2-吡咯烷甲醇（1），是一种有效的有机催化剂，能以优异的非对映选择性和对映选择性促进醛的多种交叉羟醛缩合反应。乙醛可作为合适的亲核醛使用。成功的亲电醛包括乙醛酸乙酯、氯乙醛、二氯乙醛、三氯乙醛、α-烷基-α-氧代醛、三氟乙醛、乙二醛、烯基醛、炔基醛和甲醛。其中一些醛以聚合物溶液、水溶液或水合形式市售可得。它们可以以市售形式直接用于不对称羟醛缩合反应，这是一个合成优势。鉴于所得到的羟醛缩合产物除了含有一个甲酰基部分外还具有多个官能团，它们是具有合成用途的手性砌块。
